Exercise-Induced Hypoxemia in Juvenile Thyroid Carcinoma With Lung Metastases.

PURPOSE: Exercise-induced arterial hypoxemia (EIAH) has been reported in patients with juvenile thyroid cancer treated with radioiodine for lung metastases. This retrospective study tested the hypothesis that EIAH is due to ventilation-perfusion-mismatch in this rare pulmonary condition. METHOD: 50 patients (age 13-23 years) treated for juvenile thyroid carcinoma and lung metastasis with 131I and 24 controls with thyroid cancer but without lung metastases and prior 131I-treatment were assessed in a state of acute hypothyroidism by com-puted tomography of the lungs, pulmonary function testing, cardiopulmonary exercise test with measurements of gas exchange, oxygen saturation, alveolar-arterial difference in pO2 (p(A-a)O2) and pCO2 (p(ET-a)CO2). RESULTS: 10 of the 50 patients with lung metastases showed EIAH. They had more pronounced pulmonary fibrosis on computed tomography, a widened p(A-a)O2, and p(ET-a)CO2, a lower DVE/DVCO2-slope, a lower respiratory rate and no increased dead space ventilation. A more pronounced EIAH was associated with male gender, younger age, lower diffusion capacity, higher p(ET-a)CO2 during exercise and a higher peak exercise tidal volume over vital capacity ratio. CONCLUSION: EIAH in patients with thyroid carcinoma and pulmonary metastases is not related to ventilation-perfusion mismatch but to alveolar hypoventilation, possibly related to an increased work of breathing with pulmonary fibrosis.

Therapy of 645 children with parapneumonic effusion and empyema-A German nationwide surveillance study.

OBJECTIVE: To evaluate the initial management of pediatric parapneumonic effusion or pleural empyema (PPE/PE) with regard to length of hospital stay (LOS). METHODS: Collection of pediatric PPE/PE cases using a nationwide surveillance system (ESPED) from 10/2010 to 06/2013, in all German pediatric hospitals. Inclusion of PPE/PE patients <18 years of age requiring drainage or with a PPE/PE persistence >7 days. Staging of PPE/PE based on reported pleural sonographic imaging. Comparison of LOS after diagnosis between children treated with different forms of initial invasive procedures performed ≤3 days after PPE/PE diagnosis: pleural puncture, draining catheter, intrapleural fibrinolytic therapy, surgical procedures. RESULTS: Inclusion of 645 children (median age 5 years); median total LOS 17 days. Initial therapy was non-invasive in 282 (45%) cases and invasive in 347 (55%) cases (pleural puncture: 62 [10%], draining catheter: 153 [24%], intrapleural fibrinolytic therapy: 89 [14%], surgical procedures: 43 [7%]). LOS after diagnosis did not differ between children initially treated with different invasive procedures. Results remained unchanged when controlling for sonographic stage, preexisting diseases, and other potential confounders. Repeated use of invasive procedures was observed more often after initial non-invasive treatment or pleural puncture alone than after initial pleural drainage, intrapleural fibrinolytic therapy or surgery. CONCLUSIONS: Initial treatment with intrapleural fibrinolytic therapy or surgical procedures did not result in shorter LOS than initial pleural puncture alone. Larger prospective studies are required to investigate which children benefit significantly from more intensive forms of initial invasive treatment. Pediatr Pulmonol. 2017;52:540-547. © 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.

Self-gated Non-Contrast-enhanced Functional Lung MR Imaging for Quantitative Ventilation Assessment in Patients with Cystic Fibrosis.

Purpose To assess the clinical feasibility of self-gated non-contrast-enhanced functional lung (SENCEFUL) magnetic resonance (MR) imaging for quantitative ventilation (QV) imaging in patients with cystic fibrosis (CF). Materials and Methods Twenty patients with CF and 20 matched healthy volunteers underwent functional 1.5-T lung MR imaging with the SENCEFUL imaging approach, in which a two-dimensional fast low-angle shot sequence is used with quasi-random sampling. The lungs were manually segmented on the ventilation-weighted images to obtain QV measurements, which were compared between groups. QV values of the patients were correlated with results of pulmonary function testing. Three radiologists rated the images for presence of ventilation deficits by means of visual inspection. Mann-Whitney U tests, receiver operating characteristic analyses, Spearman correlations, and Gwet agreement coefficient analyses were used for statistical analysis. Results QV of the entire lungs was lower for patients with CF than for control subjects (mean ± standard deviation, 0.09 mL/mL ± 0.03 vs 0.11 mL/mL ± 0.03, respectively; P = .007). QV ratios of upper to lower lung halves were lower in patients with CF than in control subjects (right, 0.84 ± 0.2 vs 1.16 ± 0.2, respectively [P < .001]; left, 0.88 ± 0.3 vs 1.11 ± 0.1, respectively [P = .017]). Accordingly, ventilation differences between the groups were larger in the upper halves (Δ = 0.04 mL/mL, P ≤ .001-.002). QV values of patients with CF correlated with forced vital capacity (r = 0.7; 95% confidence interval [CI]: 0.21, 0.91), residual volume (static hyperinflation, r = -0.8; 95% CI: -0.94, 0.42), and forced expiratory volume in 1 second (airway obstruction, r = 0.7; 95% CI: 0.21, 0.91). Disseminated small ventilation deficits were the most frequent involvement pattern, present in 40% of the functional maps in CF versus 8% in the control subjects (P < .001). Conclusion SENCEFUL MR imaging is feasible for QV assessment. Less QV, especially in upper lung parts, and correlation to vital capacity and to markers for hyperinflation and airway obstruction were found in patients with CF. © RSNA, 2016.

P67-phox (NCF2) lacking exons 11 and 12 is functionally active and leads to an extremely late diagnosis of chronic granulomatous disease (CGD).

Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000 + 2T → G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage.

Prediction of tumour regrowth of pontine glioma using a two-term model.

BACKGROUND: Modelling tumour regrowth kinetics and determining tumour burden is critically important in making accurate patient prognoses. PATIENTS AND METHODS: Our two-term model, which describes tumour regrowth after chemotherapy was tested by analyzing tumour sizes in patients with pontine gliomas treated at a major cancer centre during the past 40 years. Tumour measurements at four early time points were used to fit the model, which was then used to predict later tumour sizes. The predictions were compared with observed measurements from clinical charts and this model's performance was compared to that of a quadratic model. RESULTS: The mean of relative errors using the two-term model was 0.186; standard deviation, 0.176. For the quadratic model, the mean of relative errors was 0.412; standard deviation, 0.521. CONCLUSION: The two-term model fits the tumour regrowth data reasonably well and is more accurate than a competing quadratic model used in the same way (p < 0.05).

Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors.

Besides of its functional role in the nervous system, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of cardiovascular function. Therefore, PACAP is a potent vasodilator in several vascular beds, including the renal vasculature. Because the kidney expresses both PACAP and PACAP-binding sites, it was speculated that PACAP might regulate cardiovascular function by direct vascular effects and indirectly by regulating renin release from the kidneys. PACAP (1-27) stimulated renin secretion from isolated perfused kidneys of rats 4.9-fold with a half-maximum concentration of 1.9 nmol/L. In addition, PACAP stimulated renin release and enhanced membrane capacitance of isolated juxtaglomerular cells, indicating a direct stimulation of exocytotic events. The effect of PACAP on renin release was mediated by the specific PACAP receptors (PAC1), because PACAP (1-27) applied in concentrations in the physiologic range (10 and 100 pmol/L) did not enhance renin release from isolated kidneys of PAC1 receptor knockout mice (PAC1-/-), whereas it stimulated renin release 1.38- and 2.5-fold in kidneys from wild-type mice. Moreover, plasma renin concentration was significantly lower in PAC1-/- compared with their wild-type littermates under control conditions as well as under a low- or high-salt diet and under treatment with the angiotensin-converting enzyme inhibitor ramipril, whereas no differences in plasma renin concentration between the genotypes were detectable after water deprivation. These data show that PACAP acting on PAC1 receptors potently stimulates renin release, serving as a tonic enhancer of the renin system in vivo.

Blood pressure-dependent inhibition of Renin secretion requires A1 adenosine receptors.

Renal perfusion pressure (RPP) regulates renin release with a reduction of RPP stimulating and an elevation inhibiting renin secretion. The precise sensing and effector mechanisms by which changes in arterial pressure are linked to the exocytosis of renin are not well-defined. The present experiments were designed to study the potential role of adenosine as a mediator of this renal baroreceptor mechanism. In isolated perfused mouse kidneys a stepwise reduction of RPP from 90 mm Hg to 65 and 40 mm Hg stimulated renin secretion rates (RSR) 1.4-fold and 3.6-fold, whereas stepwise elevations of RPP from 90 mm Hg to 115 and 140 mm Hg suppressed RSR to 64% or 40% of baseline. Inactivation of A1 adenosine receptors by either pharmacological blockade (DPCPX 1 micromol/L) or genetic deletion (A1AR(-/-) mice) did not modify the stimulation of renin release by a low RPP, but completely prevented the suppression of renin secretion by higher perfusion pressures. In vivo, the induction of arterial hypertension by either acute (single subcutaneous injection) or chronic (osmotic minipump for 72 hours) application of phenylephrine significantly reduced plasma renin concentration (PRC) in wild-type mice to approximately 40% of control, whereas it did not significantly affect PRC in A1AR(-/-) mice. Together these data demonstrate that A1 adenosine receptors are indispensable for the inhibition of renin secretion by an increase in blood pressure, suggesting that formation and action of adenosine is responsible for baroreceptor-mediated inhibition of renin release. In contrast, the stimulation of the renin system by a low blood pressure appears to follow different pathways.